A limitation of the present study is that no genome wide sequencing has been applied to patient DNA, so the HAE subtype was diagnosed on the basis of the identification of known pathogenic variants of F12 or PLG. Very rare combinations of pathogenic variants of different genes were not considered, although C1-INH levels were in the normal range in our HAE-nC1-INH sample (Table 1). This evidence concerns the gene SERPING1 and hereditary angioedema.